de Moraes Rodolfo Pacheco, Pimenta Ruan, Mori Fernando Noboru Cabral, Dos Santos Gabriel Arantes, Viana Nayara Izabel, Guimarães Vanessa Ribeiro, de Camargo Juliana Alves, Leite Katia Ramos Moreira, Srougi Miguel, Nahas William Carlos, Reis Sabrina T
Laboratory of Medical Investigation (LIM55), Urology Department, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
D'Or Institute for Research and Education (IDOR), São Paulo, Brazil.
Mol Biol Res Commun. 2021 Dec;10(4):149-156. doi: 10.22099/mbrc.2021.40912.1646.
Prostate cancer is the most frequent malignancy affecting men worldwide. Due to the low sensitivity and specificity of the prostate-specific antigen test and the digital rectal exam as screening modalities, several alternatives are being studied. This study aimed to evaluate the application of MMP-9 and its regulators (TIMP-1, RECK, and miR-338-3p) as diagnostic and prognostic indicators of prostate cancer. A total of 134 randomly selected patients under investigation for prostate cancer submitted to a transrectal ultrasound-guided prostate biopsy were enrolled in the study; of these, 61 were positive for the disease (cases), and 73 were negative (control group). The tissue samples were further analyzed by gene and miR-338-3p expression analysis using qRT-PCR (one randomly selected fragment of each patient). Approximately 58% of the patients with prostate cancer presented MMP9 upregulation, while 73%, 65%, and 69% downregulated IMP-1, RECK, and miR-338-3p, respectively. MiR-338-3p was expressed at lower levels in patients with PSA concentrations exceeding 20 ng/mL (p=0.045) and abnormal DRE (p=0.006), while the RECK was more expressed in patients with abnormal DRE (p=0.01). We found that most patients with prostate cancer overexpressed MMP-9; on the other hand, most of them underexpressed TIMP-1, RECK, and miR-338-3p. MiR-338-3p presented as a possible predictor of poor prognosis. Further studies are warranted to evaluate these biomarkers as prognosis factors better.
前列腺癌是全球男性中最常见的恶性肿瘤。由于前列腺特异性抗原检测和直肠指检作为筛查方式的敏感性和特异性较低，目前正在研究几种替代方法。本研究旨在评估基质金属蛋白酶-9（MMP-9）及其调节因子（组织金属蛋白酶抑制剂-1（TIMP-1）、富含半胱氨酸的分泌性蛋白（RECK）和微小RNA-338-3p（miR-338-3p））作为前列腺癌诊断和预后指标的应用。共有134例随机选择的接受经直肠超声引导下前列腺穿刺活检的前列腺癌患者纳入本研究；其中，61例疾病呈阳性（病例组），73例呈阴性（对照组）。使用定量逆转录聚合酶链反应（qRT-PCR）对组织样本进行基因和miR-338-3p表达分析（每个患者随机选择一个片段）。约58%的前列腺癌患者出现MMP9上调，而分别有73%、65%和69%的患者TIMP-1、RECK和miR-338-3p下调。在前列腺特异性抗原（PSA）浓度超过20 ng/mL（p=0.045）和直肠指检异常（p=0.006）的患者中，miR-338-3p表达水平较低，而在直肠指检异常的患者中RECK表达较高（p=0.01）。我们发现大多数前列腺癌患者MMP-9过表达；另一方面，他们中的大多数TIMP-1、RECK和miR-338-3p表达不足。miR-338-3p可能是预后不良的预测指标。有必要进一步研究以更好地评估这些生物标志物作为预后因素的作用。
